2LZ6

Distinct ubiquitin binding modes exhibited by sh3 domains: molecular determinants and functional implications

2LZ6 の概要

• エントリーDOI: 10.2210/pdb2lz6/pdb
• 関連するPDBエントリー: 2LZ7
• NMR情報: BMRB: 18737
• 分子名称: Ubiquitin, CD2-associated protein (2 entities in total)
• 機能のキーワード: signaling protein
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Ubiquitin: Cytoplasm : P0CG48; Cytoplasm, cytoskeleton: Q9JLQ0
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 15723.74

構造登録者

Ortega-Roldan, J.,Azuaga, A.,Blackledge, M.,Van Nuland, N. (登録日: 2012-09-24, 公開日: 2013-10-02, 最終更新日: 2024-05-15)

主引用文献

Ortega Roldan, J.L.,Casares, S.,Ringkjbing Jensen, M.,Cardenes, N.,Bravo, J.,Blackledge, M.,Azuaga, A.I.,van Nuland, N.A.
Distinct Ubiquitin Binding Modes Exhibited by SH3 Domains: Molecular Determinants and Functional Implications.
Plos One, 8:e73018-e73018, 2013

PubMed Abstract: SH3 domains constitute a new type of ubiquitin-binding domains. We previously showed that the third SH3 domain (SH3-C) of CD2AP binds ubiquitin in an alternative orientation. We have determined the structure of the complex between first CD2AP SH3 domain and ubiquitin and performed a structural and mutational analysis to decipher the determinants of the SH3-C binding mode to ubiquitin. We found that the Phe-to-Tyr mutation in CD2AP and in the homologous CIN85 SH3-C domain does not abrogate ubiquitin binding, in contrast to previous hypothesis and our findings for the first two CD2AP SH3 domains. The similar alternative binding mode of the SH3-C domains of these related adaptor proteins is characterised by a higher affinity to C-terminal extended ubiquitin molecules. We conclude that CD2AP/CIN85 SH3-C domain interaction with ubiquitin constitutes a new ubiquitin-binding mode involved in a different cellular function and thus changes the previously established mechanism of EGF-dependent CD2AP/CIN85 mono-ubiquitination.

PubMed: 24039852
DOI: 10.1371/journal.pone.0073018

実験手法

SOLUTION NMR